Tuberculosis (TB) is a common and serious complication of human immunodeficiency virus-type 1 (HIV) infection in the developing world, especially in sub-Saharan Africa. Since the emergence of the HIV epidemic in Africa, the incidence rates of TB have risen dramatically, overwhelming national TB control programs across Africa. Over one-half of TB patients presenting to TB clinics in Africa are HIV-infected, often presenting in early stages of HIV infection. Recent WHO guidelines on the management of HIV-associated pulmonary TB recommend antiretroviral (ARV) therapy in patients with CD4+ T cells < 200 cells/muL but not for HIV-infected TB patients who present with high CD4+ cells. In Uganda, over half of HIV-infected patients with active TB present with CD4+ counts above 200 cells/?L. There are clinical and scientific reasons for treating these TB patients with ARV therapy even when they present in early stages of HIV infection. First, mortality in HIV-associated TB is high, even when patients respond to effective anti-tuberculous therapy. Second, excess mortality associated with TB is most evident when CD4+ counts are above 200 cell/muL. Third, in dually-infected patients, TB results in prolonged immune activation which may enhance viral replication and accelerate the decline of CD4+ cells. The proposed study will test whether a novel approach of punctuated ARV therapy given during treatment of active TB will slow progression of HIV disease in TB patients with CD4+ cells > 350 cells/muL. The study will also assess the possible risks (e.g., drug toxicities and resistance) and benefits (e.g., more rapid clearance of MTB and reduced TB relapse) of punctuated ARV therapy. The Specific Aims of this proposal will be addressed in an open label, randomized, clinical trial of HIV-infected TB patients (CD4+ greater than or equal too 350 cells/muL) with a concurrent, nonrandomized, observational comparison group of HIV-infected persons without active TB (CD4+ greater than or equal too 350 cells/muL). We will compare rates of CD4+ cell count decline over 2 years between TB patients who are randomized to either immediate, punctuated ARV therapy given for six months during TB treatment or delayed ARV therapy which is started when CD4+ cell counts fall below 200 cells/?L. We will also compare the rates of CD4+ cell count decline among TB patients with a concurrent, observational comparison group of patients with CD4+ counts greater than or equal too 350 cells/muL without TB to quantify the extent to which CD4+ cell decline is accelerated with active TB and to determine the extent to which the decline is neutralized in patients who receive punctuated ARV therapy. The research team from the Uganda-Case Western Reserve Research Collaboration and the Antiviral unit at the University of California, San Diego has the necessary experience in clinical trials, TB and HIV pathogenesis, and antiretroviral therapy to complete the study.